Proteinases Related to the Bone Destruction and those Inhibitors in Human Cholesteatoma of the Middle ear

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Objective: We examined metalloproteinase-1 (MMP-1), cathepsin L, and inhibitors (tissue inhibitor of metalloproteinse-1 (TIMP-1), cystatin A, and Cu- and Zn-containing superoxide dismutase (Cu, Zn-SOD)) in human cholesteatoma of the middle ear. Using the above data, epithelia and subepithelial granulation was discussed.Method: Cathepsin L activity in the cholesteatoma epithelium, granulation tissues in cholesteatoma, or granulation tissues in noncholesteatoma were measured using Barrett's method. Cystatin A expressions were observed by Western blot analysis. Moreover, MMP-1, TIMP-1, cathepsin L, and Cu, Zn-SOD were examined immunohistochemically.Results: Although, MMP-1 and cathepsin L immunohistochemically showed both epithelial and subepithelial granulation, the mean cathepsin L activity was higher in subepithelial than epithelial granulation. Subepithelial granulations with high cathepsin L activity resulted in extensive bone destruction in cholesteatomas. Cystain A and Cu, Zn-SOD with inhibitors of MMP-1 and cathepsin L were more strongly positive in epithelial regions than in subepithelial granulation tissues.Conclusion: These results suggest that the area related to bone destruction in human cholesteatoma is subepithelial granulation rather than epithelia.